The research outlined in this proposal is directed toward the continued development of a system which combines genetic and biochemical approaches for the analysis of DNA repair and mutagenesis in the complex eukaryote, Drosophila melanogaster. Our genetic approach focuses on the isolation and characterization of mutagen-sensitive strains and is based on the rationale that mutagen sensitivity may reflect defects in DNA repair functions. Experiments are designed to isolate specific mutant strains which will serve to identify all of the loci in the genome which are involved with mutagen sensitivity. Genetic tests of the mutant strains will include complementation analysis and mapping studies to identify specific loci; studies of mutagen cross-sensitivities and epistatic interactions to determine the inter-relationships of different mutant loci; survival studies as indirect measures of defects in DNA repair capacity; and, mutagenesis experiments to determine the effects of various mutations on the mutagenic process. Our biochemical approach focuses on studies of DNA repair capacities in control versus mutagen-sensitive strains. Assays to detect defects in excision or postreplication repair ability as described. These studies offer the hope that the genetic and biochemical bases of mutation and DNA repair can be outlined for a complex eukaryotic system. Continued characterization of these mutagen-sensitive strains will lead to the development of more sophisticated methods for the analysis of environmental chemicals for potential mutagenic activity.